Evidence map›Paper›PMID 38915549›Full record

ArticlebioRxiv : the preprint server for biology2024

Lipid-siRNA conjugate accesses perivascular transport and achieves durable knockdown throughout the central nervous system.

Alexander G Sorets, Katrina R Schwensen, Nora Francini, Andrew Kjar, Adam M Abdulrahman, Alena Shostak, Ketaki A Katdare, Kathleen M Schoch, Rebecca P Cowell, Joshua C Park and 12 more

Abstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in bioRxiv : the preprint server for biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

22 authors.

Alexander G SoretsDepartment of Biomedical Engineering, Vanderbilt University, Nashville, TN, USA.
Katrina R SchwensenDepartment of Chemical and Biomolecular Engineering, Vanderbilt University, Nashville, TN, USA.
Nora FranciniDepartment of Biomedical Engineering, Vanderbilt University, Nashville, TN, USA.
Andrew KjarDepartment of Biomedical Engineering, Vanderbilt University, Nashville, TN, USA.
Adam M AbdulrahmanDepartment of Biomedical Engineering, Vanderbilt University, Nashville, TN, USA.
Alena ShostakDepartment of Neurology, Vanderbilt University Medical Center, Nashville, TN, USA.
Ketaki A KatdareVanderbilt Brain Institute, Vanderbilt University, Nashville, TN, USA.
Kathleen M SchochDepartment of Neurology, Washington University School of Medicine in St. Louis, St. Louis, MO, USA.
Rebecca P CowellDepartment of Chemical and Biomolecular Engineering, Vanderbilt University, Nashville, TN, USA.
Joshua C ParkDepartment of Biomedical Engineering, Vanderbilt University, Nashville, TN, USA.
Alexander P LigockiDepartment of Chemical and Biomolecular Engineering, Vanderbilt University, Nashville, TN, USA.
William T FordDepartment of Biomedical Engineering, Vanderbilt University, Nashville, TN, USA.
Lissa Ventura-AntunesDepartment of Neurology, Vanderbilt University Medical Center, Nashville, TN, USA.
Ella N HoogenboezemDepartment of Biomedical Engineering, Vanderbilt University, Nashville, TN, USA.
Alex PruskyDepartment of Neurology, Vanderbilt University Medical Center, Nashville, TN, USA.
Mark CastleberryDepartment of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.
Danielle L MichellDepartment of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.
Timothy M MillerDepartment of Neurology, Washington University School of Medicine in St. Louis, St. Louis, MO, USA.
Kasey C VickersDepartment of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.
Matthew S SchragVanderbilt Brain Institute, Vanderbilt University, Nashville, TN, USA.ORCID 0000-0001-7048-0503
Craig L DuvallDepartment of Biomedical Engineering, Vanderbilt University, Nashville, TN, USA.
Ethan S LippmannDepartment of Biomedical Engineering, Vanderbilt University, Nashville, TN, USA.

Funding

Tumor Immunology and Microenvironment Research ProgramP30CA068485 · NCI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI STACIE B DUSETZINA · 1995 to 2026
$172.8M
Vanderbilt Institute for Clinical and Translational Research (VICTR) -Identifying correlates of functional immunity in SARS-CoV-2 convalescent plasmaUL1TR002243 · NCATS · VANDERBILT UNIVERSITY MEDICAL CENTER · PI Paul A. Harris, Wesley H Self · 2017 to 2026
$130.7M
VANDERBILT UNIVERSITY CTSA FOR PEDIATRIC RESEARCHUL1RR024975 · NCRR · VANDERBILT UNIVERSITY · PI BERNARD, GORDON RAPHAEL · 2007 to 2011
$45.7M
Translational Analysis CoreP30DK058404 · NIDDK · VANDERBILT UNIVERSITY MEDICAL CENTER · PI RICHARD M. PEEK · 2002 to 2026
$29.9M
Shop Module CoreP30EY008126 · NEI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI David J. Calkins · 1989 to 2026
$19.6M
TRAINING PROGRAM IN ENVIRONMENTAL TOXICOLOGYT32ES007028 · NIEHS · VANDERBILT UNIVERSITY · PI F PETER Guengerich, Fiona Edith Harrison · 1985 to 2026
$15.7M
VANTAGE:Consolidation to create the Vanderbilt Technologies for Advanced GenomicsG20RR030956 · NCRR · VANDERBILT UNIVERSITY · PI PIETENPOL, JENNIFER A · 2010 to 2010
$8.7M
Perivascular fibroblasts, vascular fibrosis, and their contributions to cerebral amyloid angiopathyRF1NS130334 · NINDS · VANDERBILT UNIVERSITY · PI LIPPMANN, ETHAN, SCHRAG, MATTHEW · 2022 to 2025
$3.9M
NextGen RNAi Delivery to Breast Tumors for Selective mTORC2 BlockadeR01CA224241 · NCI · VANDERBILT UNIVERSITY · PI BRANTLEY-SIEDERS, DANA M, COOK, REBECCA SARA · 2018 to 2022
$2.5M
Albumin hitchhiking siRNAs for gene targeting in aged brainR21AG077807 · NIA · VANDERBILT UNIVERSITY · PI DUVALL, CRAIG LEWIS, LIPPMANN, ETHAN · 2022 to 2023
$420k
NCATS NIH HHS UL1 TR002243NCI NIH HHS P30 CA068485NCI NIH HHS R01 CA224241NCRR NIH HHS G20 RR030956NCRR NIH HHS UL1 RR024975NEI NIH HHS P30 EY008126NIA NIH HHS R21 AG077807NIDDK NIH HHS P30 DK058404NIEHS NIH HHS T32 ES007028NINDS NIH HHS RF1 NS130334
6 · The paper itself

Abstract

Short-interfering RNA (siRNA) has gained significant interest for treatment of neurological diseases by providing the capacity to achieve sustained inhibition of nearly any gene target. Yet, efficacious drug delivery throughout deep brain structures of the CNS remains a considerable hurdle for intrathecally administered therapeutics. We herein describe an albumin-binding lipid-siRNA conjugate that transports along meningeal and perivascular CSF pathways, leading to broad dispersion throughout the CNS parenchyma. We provide a detailed examination of the temporal kinetics of gene silencing, highlighting potent knockdown for up to five months from a single injection without detectable toxicity. Single-cell RNA sequencing further demonstrates gene silencing activity across diverse cell populations in the parenchyma and at brain borders, which may provide new avenues for neurological disease-modifying therapies.

Indexed as

central nervous systemcerebrospinal fluiddrug deliverygene therapysiRNA

Identifiers

PMID38915549
PMCPMC11195074

What OpenQuestion holds

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LicenceCC BY-NC-ND
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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.